Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[8] The various species range from lean to fatty and their oil content in the tissues has been shown to vary from 0.7% to 15.5%.[9] They also differ in their effects on organ lipids.[8] Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish, and serum omega−3 fatty acid concentrations.[10] Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA.[10]

Often marketed and sold for consumption as part of the diet or in dietary supplements in contemporary societies, fish oils also have found roles in external use, as emollients[18] or as general ointments[19] as well as in body art,[20] or for alleged insulation against cold.[21]

The effect of fish oil consumption on prostate cancer is controversial,[26][27] as one study showed decreased risk with higher blood levels of DPA, whereas another reported increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA.[28] Some evidence indicated an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk.[29]

Fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[3][4][5][11] Earlier, in 2007, the American Heart Association had recommended the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautioned pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish.[30] (Optimal dosage was related to body weight.)

The US National Institutes of Health lists three conditions for which fish oil and other omega-3 sources are most highly recommended: hypertriglyceridemia (high triglyceride level), preventing secondary cardiovascular disease, and hypertension (high blood pressure). It then lists 27 other conditions for which there is less evidence. It also lists possible safety concerns: "Intake of 3 grams per day or greater of omega-3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil/omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke."[17]

There have been some human trials that have concluded that consuming omega-3 fatty acids slightly reduces blood pressure (DHA could be more effective than EPA). It is important to note that because omega-3 fatty acids can increase the risk of bleeding, a qualified healthcare provider should be consulted before supplementing with fish oil.[36]

A 2008 Cochranesystematic review found that limited data is available. In the one eligible study, omega-3s were an effective adjunctive therapy for depressed but not manic symptoms in bipolar disorder. The authors found an "acute need" for more randomised controlled trials.[37]

A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced less depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[38]

In a 2011 meta-analysis of PubMed articles about fish oil and depression from 1965 to 2010, researchers found that "nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias."[39]

A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."[40]

A Cochranemeta-analysis published in June 2012 found no significant protective effect for cognitive decline for those aged 60 and over and who started taking fatty acids after this age. A co-author of the study said to Time, "Our analysis suggests that there is currently no evidence that omega-3 fatty acid supplements provide a benefit for memory or concentration in later life".[41]

Some studies reported better psychomotor development at 30 months of age in infants whose mothers received fish oil supplements for the first four months of lactation.[43] In addition, five-year-old children whose mothers received modest algae based docosahexaenoic acid supplementation for the first 4 months of breastfeeding performed better on a test of sustained attention. This suggests that docosahexaenoic acid intake during early infancy confers long-term benefits on specific aspects of neurodevelopment.[43]

In addition, provision of fish oil during pregnancy may reduce an infant’s sensitization to common food allergens and reduce the prevalence and severity of certain skin diseases in the first year of life. This effect may persist until adolescence with a reduction in prevalence and/or severity of eczema, hay fever and asthma.[44]

Fish oil is a commonly used dietary supplement, with sales in the U.S. alone reaching $976 million in 2009.[46] Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems include contamination, inaccurate listing of EPA and DHA levels, spoilage and formulation issues.[47]

Fish can accumulate toxins such as mercury, dioxins, and polychlorinated biphenyls (PCBs), and spoiled fish oil may produce peroxides.[48] There appears to be little risk of contamination by microorganisms, proteins, lysophospholipids, cholesterol, and trans-fats.[49]

Dioxins and PCBs may be carcinogenic at low levels of exposure over time. These substances are identified and measured in one of two categories, dioxin-like PCBs and total PCBs. While the U.S. FDA has not set a limit for PCBs in supplements, the Global Organization for EPA and DHA (GOED) has established a guideline allowing for no more than 3 picograms of dioxin-like PCBs per gram of fish oil. In 2012, samples from 35 fish oil supplements were tested for PCBs. Trace amounts of PCBs were found in all samples, and two samples exceeded the GOED‘s limit.[52] Although trace amounts of PCBs contribute to overall PCB exposure, Consumerlab.com claims the amounts reported by tests it ordered on fish oil supplements are far below those found in a single typical serving of fish.[53]

Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[49] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]

The American Heart Association recommends 250–500 mg/day of EPA and DHA.[54] In the United States the FDA recommends not exceeding 3 grams per day of EPA and DHA omega-3 fatty acids, with no more than 2 grams per day from a dietary supplement.[55]

According to independent laboratory[which?] tests, the concentrations of EPA and DHA in supplements can vary from between 8 and 80% fish oil content. The concentration depends on the source of the omega-3s, how the oil is processed, and the amounts of other ingredients included in the supplement.[52] A 2012 report claims 4 of 35 fish oil supplements it covered contained less[quantify] EPA or DHA than was claimed on the label, and 3 of 35 contained more[quantify][52] A ConsumerLab.com publication in 2010 claims 3 of 24 fish oil supplements it covered contained less[quantify] EPA and/or DHA than was claimed on the label.[46] However, the bioavailability of EPA and DHA from both capsular and emulsified fish oils has been shown to be high.[56]

Fish oil supplements are available as liquids, capsules, and tablets. Some pills are enteric-coated to help prevent indigestion or "fish burps", however; enteric-coated products have the potential to release ingredients too early or late in the digestive process. In 2010 ConsumerLab.com reports that one of 24 fish oil supplements[which?] with enteric-coated pill released ingredients prematurely[clarification needed] ; Consumerlab.com claims in its publication that there were problems in results of tests it ordered in 2012.[46]

Fish oil preparations that are only available with a doctor's prescription undergo the same FDA regulatory requirements as other prescription pharmaceuticals, with regard to both efficacy and safety.[57]

The FDA says it is safe to take up to 3000 mg of omega-3 per day.[59] (This is not the same as 3000 mg of fish oil. A 1000 mg pill typically has only 300 mg of omega-3; 10 such pills would equal 3000 mg of omega-3.) Dyerberg studied healthy Greenland Inuit and found an average intake of 5700 mg of omega-3 EPA per day.[60] According to the European Food Safety Authority's (EFSA) Panel on Dietetic Products, Nutrition and Allergies, supplementation of 5 grams of EPA and DHA combined does not pose a safety concern for adults.[61]

The liver and liver products (such as cod liver oil) of fish and many animals (such as seals and whales) contain omega-3, but also the active form of vitamin A. At high levels, this form of the vitamin can be dangerous (Hypervitaminosis A).[62]

Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[63][64] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[65]

A March 2010 lawsuit filed by a California environmental group claimed that eight brands of fish oil supplements contained excessive levels of PCB's, including CVS/pharmacy, Nature Made, Rite Aid, GNC, Solgar, Twinlab, Now Health, Omega Protein and Pharmavite. The majority of these products were either cod liver or shark liver oils. Those participating in the lawsuit claim that because the liver is the major filtering and detoxifying organ, PCB content may be higher in liver-based oils than in fish oil produced from the processing of whole fish.[66][67]

An analysis based on data from the Norwegian Women and Cancer Study (NOWAC) with regards to the dangers of persistent organic pollutants (POPs) in cod liver came to the conclusion that "in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found."[68]

A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free."[69]

Microalgae oil is a vegetarian alternative to fish oil. Supplements produced from microalgae oil provide a balance of omega-3 fatty acids similar to fish oil, with a lower risk of pollutant exposure.[70]

^Heartney, Eleanor (2007). "Zhang Huan: Becoming the Body". Zhang Huan: Altered States. Charta and Asia Society. ISBN978-8881586417. Retrieved 2014-10-23. This becomes abundantly clear in the work of Chinese body artist Zhang Huan. In the course of his career, Zhang Huan has subjected himself to painful trials: sitting motionless for hours in an outhouse covered in honey and fish oil while flies crawled over his body [...].

^Martins, Julian G (2009). "EPA but Not DHA Appears to Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials". Journal of the American College of Nutrition. 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID20439549.

Joyce A. Nettleton, ed. "PUFA Newsletter". Retrieved 20 February 2006. Two newsletters, both quarterly, reviewing recent publications in essential fatty acids. One is written for researchers, the second is for consumers. Industry sponsored, academic contributors.